tbuckley/cabot-search huggingface dataset:
Abstract 11349: Longitudinal Analysis of Cardiac Biomarkers and Renal Function in Transthyretin Cardiac Amyloidosis: Association With Mortality and Tafamidis Use
Authors: Jingwen Zhang, Priyanka T Bhattacharya, Sergio Teruya, Stephen Helmke, Mathew S Maurer
Journal: Circulation (2022)

Introduction: Biomarkers have prognostic value in transthyretin amyloid cardiomyopathy (ATTR-CM). However, their temporal trends and the impact of tafamidis use on biomarkers have not been well-described. Hypothesis: There are differences in the trajectory of cardiac biomarkers and estimated glomerular filtration rate (eGFR) in ATTR-CM patients who died compared to those who survived and among those who did or did not receive tafamidis. Methods: This was a retrospective study of consecutive ATTR-CM patients referred to Columbia University Medical Center with ≥3 years of biomarker data. We plotted individual data over time in each cohort (alive vs. dead, tafamidis vs. no tafamidis) and fitted exponential regression slopes for each using linear mixed effects modeling. Results: Patients who died had a higher average baseline NT-proBNP and troponin and lower eGFR than patients who survived. Baseline median (IQR) NT-proBNP in pg/mL was 2847 (1131, 5011) and increased to 6127 (2874, 13184) prior to death, while for patients who survived, the median was 1151 (641, 3080) at baseline and 1415 (791, 2856) at last follow-up. Median (IQR) troponin T in ng/mL was 0.038 (0.020, 0.053) at baseline and 0.080 (0.050, 0.149) prior to death, while in patients who survived, the median was 0.030 (0.010, 0.043) at baseline and 0.037 (0.024, 0.043) at last follow-up. The rate of increase of troponin T and NT-proBNP was greater in the patients who died than patients who survived (p&lt;0.0001). During this period, eGFR fell 14.3% from baseline in patients who died and 8.6% in patients who survived. There were no apparent differences in the trajectory of these biomarkers between patients with and without tafamidis treatment. Conclusions: Serial analysis of cardiac and renal biomarkers shows substantial heterogeneity of these measures. The trajectories of biomarkers differed over 3 years before death. Tafamidis use in the real world was not associated with changes in biomarkers and eGFR over time.
Abstract 11295: Design and Rationale for the BETTER CARE-HF Trial: A Pragmatic Cluster-Randomized Controlled Trial Comparing Two Targeted Approaches to Ambulatory Clinical Decision Support for Cardiologists
Authors: Amrita Mukhopadhyay, Harmony Reynolds, Yuhe Xia, Lawrence M Phillips, Rod Aminian, Ruth-Ann Diah, Arielle Nagler, Adam Szerencsy, Archana Saxena, Leora Horwitz, Stuart D Katz, Saul Blecker
Journal: Circulation (2022)

Introduction: Heart failure with reduced ejection fraction (HFrEF) is a leading cause of morbidity and mortality. However, shortfalls in prescribing of proven therapies, particularly mineralocorticoid receptor antagonist (MRA) therapy, account for several thousand preventable deaths per year nationwide. Electronic clinical decision support (CDS) is a potential low-cost and scalable solution to improve prescribing of therapies. However, the optimal timing and format of CDS tools is unknown. We developed two CDS tools to inform cardiologists of gaps in MRA therapy for patients with HFrEF and without contraindication to MRA therapy: 1) a best practice alert (BPA) that notifies cardiologists at the time of patient visit, and 2) an automated in-basket message that allows for review between visits (Figure). Objective: The BETTER CARE-HF (Building Electronic Tools to Enhance and Reinforce CArdiovascular REcommendations for Heart Failure) trial aims to compare the effectiveness of a BPA vs. in-basket message vs. usual care on the primary outcome of MRA prescribing. Methods: This is a pragmatic, cluster-randomized, three-arm intervention trial. Patients are randomized as a cluster at the level of their cardiologist in a 1:1:1 fashion (180 cardiologists included). The primary outcome is MRA prescription at the end of the study period, and secondary outcomes include prescribing of other GDMT, time to prescription, and provider-level changes in prescribing rates. We will require a total of 1,503 patients (501 per arm) to detect 10% improvement in prescribing with 80% power, and estimate a trial duration of 6 months. Implications: To our knowledge, no study has directly compared the efficacy of a BPA vs. in-basket message. If effective, our findings can be rapidly disseminated to improve morbidity and mortality for patients with HFrEF, and can also inform the development of future CDS interventions for other disease states. Trial registration: NCT05275920
Abstract 11084: Procedural Parameters During Cryoballoon Ablation Predict Early Pulmonary Vein Reconnection and Atrial Fibrillation Recurrence
Authors: Yaacoub Chahine, Tanzina Afroze, Savannah Bifulco, Fima Macheret, Nashwa Abdulsalam, Patrick M Boyle, Nazem W Akoum
Journal: Circulation (2022)

Introduction: Cryoballoon ablation (CBA) is an established procedure for the management of atrial fibrillation (AF). We sought to assess procedural parameters as predictors of early PV reconnection and AF recurrence following CBA. Methods: 119 patients undergoing CBA for AF were included. Balloon temperature (BT) recorded by the console during CBA targeting each of the four pulmonary veins (PV) was monitored to determine the time needed to reach -15°C and -40°C from the start of the freeze. BT at 30 seconds (s), 60 s and the temperature nadir point were also recorded. Rewarming (thaw) time from the nadir point to 0 °C, was also determined. PVs were assessed for early reconnection and patients were followed for arrhythmia recurrence. Results: Early PV reconnection was identified in 39 (8.3%) of 471 PVs. BT was significantly colder in the absence of early PV reconnection (30 s: -33.5°C vs -29.5°C, p=0.001; 60 s: -41°C vs -36.5°C, p&lt;0.001; nadir: -47°C vs -41.5°C, p&lt;0.001). Early PV reconnection was associated with significantly shorter time to reach -15°C and -40°C (12s vs 14.5s, p=0.023; and 46s vs 75s, p=0.005) and longer rewarming time (7s vs 5.75s, p=0.012) (Panel A). A logistic regression model with the procedural parameters was created to predict early PV reconnection and the corresponding ROC analysis had an AUC=0.71 (Panel B). During an average follow-up period of 559 days, AF recurrence occurred in 51 (49%) patients. Kaplan Meier analysis showed better arrhythmia free survival for patients in whom BT decreased below -40°C in all PVs and patients who had no early PV reconnections, compared to patients where BT below -40°C was not achieved in at least one PV (Log Rank = 6.3, p=0.012) and patients who had PV reconnections (Log Rank = 4.1, p=0.043) (Panel C). Conclusions: Slower BT decline, warmer BT nadir, and faster rewarming time predict early PV reconnection. A lower rate of AF recurrence was associated with absence of early PV reconnections and achieving a BT below -40 °C in all PVs.
Abstract 11127: Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Heart Failure With Preserved Ejection Fraction and Type 2 Diabetes
Authors: Edouard L Fu, Elisabetta Patorno, Brendan Everett, Muthiah Vaduganathan, Scott Solomon, Raisa Levin, Sebastian Schneeweiss, Rishi Desai
Journal: Circulation (2022)

Introduction: Limited information exists on the effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT2i) among patients with heart failure with preserved ejection fraction (HFpEF) in routine clinical care. Further, it remains uncertain if all agents in the SGLT2i class confer similar benefits in HFpEF. Methods: We compared initiators of SGLT2i versus sitagliptin, a DPP-4 inhibitor, using US Medicare data (04/2013-12/2018). Patients were required to have a diagnosis of type 2 diabetes (T2D) and HFpEF, identified using a validated prediction model. The primary outcome was a composite of all-cause mortality or worsening HF, i.e., outpatient use of intravenous diuretics or hospitalization for heart failure (HHF). Hazard ratios (HR) were estimated using Cox regression adjusting for 121 confounders. To address potential unmeasured confounding, we calibrated our results using estimates for HHF from a meta-analysis of HF RCTs of SGLT2i. Results: We included 33,475 patients with HFpEF and T2D (6,924 initiated SGLT2i and 26,551 initiated sitagliptin). Initiation of SGLT2i was associated with a lower risk of the primary composite outcome (adjusted HR 0.60; 95% CI 0.54-0.68), all-cause mortality (0.62; 0.53-0.74) and worsening HF (0.58; 0.52-0.66). We observed similar associations with the primary outcome for 3 SGLT2i agents (p-value for interaction 0.28) and across subgroups based on demographics, comorbidities, and HF treatments (Figure). Bias calibrated HR were 0.79 (0.69-92) for the primary composite outcome and 0.81 (0.63-1.03) for all-cause mortality suggesting our results cannot be fully explained by residual confounding. Conclusions: In routine US clinical practice, SGLT2i demonstrated robust clinical effectiveness in older adults with HFpEF and T2D without apparent heterogeneity across the class. Given the observational nature of the study, potential confounding and HFrEF/HFpEF misclassification cannot be entirely ruled out.
Abstract 11351: Surgical Myectomy versus Alcohol Septal Ablation Among Patients With HOCM: A Systematic Review and Meta-Analysis
Authors: Vikash Jaiswal, Abdelrahman Attia, Kriti Kalra, Nirmit Patel, Hasitha Manohar, Akash Jaiswal, Mittal R Savaliya, Deepak Verma, abhigan babu Shrestha, Nida Khan, Yusra Nasir, Monodeep Biswas
Journal: Circulation (2022)

Background: Surgical myectomy (SM) and Alcohol septal ablation (ASA) are two known therapies recommended for symptomatic hypertrophic cardiomyopathy patients. Although, their results are contradictory between the outcomes of these two procedures to this day. Hypothesis: This meta-analysis evaluates and compares the two procedure-related clinical outcomes. Method: We performed a systematic literature search on PubMed, Embase and Cochrane for relevant articles from inception until May 20, 2022. Unadjusted odds ratios (OR) were pooled using a random-effect model, and a p-value of &lt;0.05 was considered statistically significant. Result: A total of 23 articles with 17165 patients comparing the outcomes among SM vs ASA with a mean follow-up of 44.18±24.06 months. The odds of short-term mortality [OR, 0.51(95%CI: 0.33-0.79), p = 0.002] were significantly lower in ASA group, while reintervention [OR, 2.93 (95%CI: 0.99-8.70), p = 0.05], and pacemaker implantation [OR, 1.97(95%CI: 1.28-3.03), p = 0.002] were significantly higher among ASA group compared to SM. Long term mortality [OR, 0.91(95%CI: 0.57-1.47), p = 0.71], SCD [OR, 1.55(95%CI: 0.76-3.17), p = 0.23], CVM [ OR, 0.76(95%CI: 0.39-1.46), p = 0.40], Stroke [OR, 1.24(95%CI: 0.24-6.26), p = 0.80], and MI [OR, 1.04(95%CI: 0.19-5.57), p = 0.97] were not different between both procedures. Conclusion: ASA and SM procedure for treating HOCM carries a similar risk of long-term mortality and other cardiovascular and cerebrovascular outcomes among both groups. However, ASA carries a lower incidence of short-term mortality and higher incidence of reintervention and pacemaker implantation than SM.
Abstract 11342: Prognostic Impact of Nutritional Status and Rehabilitation Education Based on Cardiopulmonary Exercise Testing in Japanese Patients With Acute Coronary Syndrome
Authors: Naoki Fujimoto, Hiroaki Murakami, Hiromasa Ito, Akihiro Takasaki, Tairo Kurita, Kaoru Dohi
Journal: Circulation (2022)

Introduction: Cardiopulmonary exercise testing (CPET) coupled with rehabilitation education improves outcomes in patients with ACS. While, malnutrition may be an under-recognized risk for poor outcomes in ACS patients. Purpose: To evaluate the prognostic factors including Controlling Nutritional Status (CONUT) score and CPET implementation on 2-year outcomes in patients with ACS in Mie Prefecture, Japan. Methods: We enrolled 3,146 ACS patients without hemodialysis using Mie ACS registry data, between 2013 and 2017. The CONUT score was measured on admission. By using CONUT score, patients were stratified into normal (0 and 1), mild risk (2-4), and moderate to severe risk (5-12) for malnutrition. Prognostic factors including exercise education based on CPET and nutritional status were determined. Results: CONUT score on admission was available in 2,621patients. 431 patients received CPET-based rehabilitation education at discharge. During the 2-year follow-up, there were 198 all-cause deaths. In the whole cohort, multivariate Cox regression analysis demonstrated that CPET implementation (hazard ratio, 0.52; p=0.047) and hemoglobin were independent negative predictors of all-cause death. While, age, male gender, hospitalization length&gt;21 days, Killip ≥2 were positively associated with death. When analyzed in patients with CONUT score, malnutrition status (mild risk: hazard ratio, 1.49; moderate to severe risk: hazard ratio, 1.86, p≤0.05) was added as a positive predictor of all-cause death. Although not statistically significant, CPET implementation had tendency toward reducing all-cause death. Conclusions: CPET implementation was the decreased 2-year risk of all-cause death in the whole cohort. As patients with higher CONUT score had worse outcomes, cardiac rehabilitation program including nutritional education was necessary even for patients with mild risk for malnutrition.
Abstract 11363: Renal Artery Velocity Time Integral is a Predictor of Improvement in Renal Function After Transcatheter Aortic Valve Implantation
Authors: Yuki Muto, Akihiko Sato, Koichiro Watanabe, Satoshi Abe, Tomofumi Misaka, Masayoshi Oikawa, ATSUSHI KOBAYASHI, Akiomi Yoshihisa, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2022)

Background: It has been reported that renal function (RF) is improved in a certain number of patients who undergo TAVI. However, the mechanisms and predictors of RF improvement remain unclear. We investigated whether preoperative renal hemodynamics assessed by intrarenal doppler ultrasonography (IRD) could predict RF improvement after TAVI. Methods and Results: We enrolled consecutive 84 patients with severe aortic stenosis (AS) who underwent TAVI in our hospital. To assess preoperative intrarenal hemodynamics, we measured renal artery velocity time integral (RA-VTI) as a marker of renal perfusion and renal venous stasis index (RVSI) as a marker of renal congestion using IRD before TAVI (Fig 1). We calculated RVSI as follows: (cardiac cycle time - venous flow time)/cardiac cycle time. RF improvement was defined as an increase &gt;10% of estimated glomerular filtration rate (eGFR) after TAVI. Of the 84 patients, 45 patients (53.5%) showed RF improvement and remaining 39 patients did not. Clinical characteristics including STS score, clinical frailty scale, comorbidities, medications, amount of contrast media and occurrence of procedural complications associated with TAVI were comparable between the two groups. In addition, laboratory data including baseline eGFR and echocardiographic parameters including severity of AS, left ventricular ejection fraction and stroke volume index were also similar between the two groups. RA-VTI determined by IRD was significantly lower in patients with RF improvement compared to those without RF improvement (34.0 ± 12.6 vs. 39.9 ± 12.5 cm, P=0.03). In contrast, there was no difference in RVSI (0.08 ± 0.13 vs. 0.05 ± 0.09, P=0.19). Logistic regression analysis indicated that RA-VTI was a predictor for RF improvement after TAVI (odds ratio 0.96, 95% confidence interval 0.93-0.99, P=0.04). Conclusions: Preoperative RA-VTI, a marker of renal perfusion, is a predictor for RF improvement after TAVI.
Abstract 112: A Transcriptomic Evaluation Of Brain And Cardiac Tissues After Cardiac Arrest In Rabbits
Authors: Yara Abi Zeid Daou, Hakim Hocini, Emilie Boissady, Estelle Faucher, Matthias Kohlhauer, fanny lidouren, Cécile Lefebre, Bijan Ghaleh, Renaud Tissier
Journal: Circulation (2022)

Introduction: A sepsis-like syndrome is known to occur rapidly after cardiac arrest. Hypothesis: A comprehensive investigation of immune signaling pathways could allow a better understanding or brain and heart disorders after cardiac arrest in rabbits. Methods: Anesthetized rabbits underwent 10 min of ventricular fibrillation. After resuscitation, they were followed during 2 or 6 h before brain and heart withdrawal (n=6 in each condition). Additional animals were submitted to a Sham procedure (n=6). The transcriptome was sequenced in cerebral and cardiac samples. Long mRNA expression was quantified vs Sham (fold-change &gt; 1.5; p&lt;0.05) before functional enrichment for pathways analysis using Reactome ID (R-HSA-9014325). Results: 403 and 1561 genes were differentially expressed at 2 and 6 h in the brain of rabbits submitted to cardiac arrest vs Sham, respectively. Those genes related to 233 and 104 signaling pathways at 2 and 6 h, among which 15 and 1 concerned innate immunity or inflammation pathways, respectively (Table). This included several pathways related to interleukins (IL-1, 4&amp;13 and 17) and toll-like receptors (TLR-1, 2, 6 and 9). In the heart, 1786 and 1457 genes were differentially expressed at 2 and 6 after cardiac arrest vs Sham. These genes were related to 68 and 58 signaling pathways at 2 and 6 h, among which only 1 and 3 concerned immunity or inflammation, respectively. Conclusion: Immuno-inflammatory events appears rapidly after cardiac arrest in the brain, supporting the need for early intervention to prevent neuro-inflammatory events. Conversely, the immuno-inflammatory response do not seem critical in the heart in the early phase after cardiac arrest. Table 1: p values of immune pathways significantly altered in either brain or heart after 2 or 6 hours after cardiac arrest, as compared to Sham animals.
Abstract 11565: Improvement in Cardiopulmonary Function in a Rat Model of Pulmonary Arterial Hypertension Observed With RKER-012, a Novel Activin Receptor Type II Ligand Trap, was Associated With Reduced Markers of Inflammation and Fibrosis in the Right Ventricle
Authors: Chris Materna, Keith Babbs, Nathan Kaplan, ffolliott Fisher, Jasbir Seehra, Jennifer Lachey
Journal: Circulation (2022)

Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary vascular resistance, impaired cardiac output, and right ventricle (RV) overload. PAH is associated with imbalanced TGF-ß signaling, marked by elevated SMAD2/3 signaling, which is associated with inflammation and fibrosis contributing to heart failure. Initially, the RV can compensate for increased pressure due to its adaptive contractility, but chronic pressure overload leads to maladaptive RV remodeling through inflammatory and fibrotic pathways. Current therapies for PAH are primarily vasodilators which do not treat the underlying pathology. RKER-012 is a research form of KER-012, an investigational modified ActRIIB ligand trap designed to inhibit signaling through SMAD2/3. We investigated RKER-012’s mechanism of prevention of cardiac pathology in a Sugen/Hypoxia (SH) PAH model. Rats received a subcutaneous (SQ) dose of 25 mg/kg Sugen 5416 under hypoxic conditions. For 3 weeks, SH rats received vehicle (SH-VEH) or 10 mg/kg RKER-012 (SH-RKER-012) twice weekly SQ. Control rats received VEH twice weekly in normoxic conditions. Systolic pulmonary arterial pressure (sPAP) and Fulton index (FI) were measured. qPCR of RV tissue was used to evaluate the mechanism of RKER-012 in this model. SH-VEH rats had increased FI and sPAP (both p≤0.0001) compared to NX, consistent with development of cardiac and pulmonary impairment. Relative to SH-VEH, RKER-012 reduced increased FIand prevented increased sPAP (both p≤0.001) in SH rats so that sPAP did not differ from NX. Relative to NX, SH-VEH had increased RV expression of fibrotic markers such as Timp1, Col1a1, Col3a1, Runx2, and LOX (all p≤0.05). In contrast, SH-RKER-012 rats had reduced expression of Timp1, Col1a1, Col3a1, Runx2 and LOX (all p≤0.05) relative to SH-VEH. Inflammation markers CD68 and MCP1 (both p≤0.05) were increased in SH-VEH compared to NX. CD68 expression was reduced in SH-RKER-012 (p≤0.01) compared to NX but MCP1 expression was not affected (p=0.54). These results support that RKER-012 attenuated upregulation of key inflammation and fibrosis markers in a PAH preclinical model and suggest that KER-012 has a distinct mechanism from vasodilation and could be developed as a cardioprotective treatment for PAH.
Abstract 11460: Sleep Duration, Quality, and Risk of Peripheral Artery Disease: Multinational Cohort and Mendelian Randomization Studies
Authors: Shuai Yuan, Michael G Levin, Olga Titova, Jie Chen, Yuhao Sun, Agneta Akesson, Xue Li, Scott M Damrauer, Susanna Larsson
Journal: Circulation (2022)

Introduction: Sleep duration and quality have been linked to atherosclerosis, however the effects on peripheral artery disease (PAD) specifically have not been well characterized. We conducted cohort, case-control, and Mendelian randomization analyses across three large multinational samples (Sweden, United Kingdom, United States) to evaluate associations between sleep traits and risk of PAD. Hypothesis: Abnormal sleep duration and poor sleep quality are associated with increased risk of PAD. Methods: Sleep traits (including duration, subjective quality, daytime napping, snoring, apnea, and insomnia) were assessed for associations with incident PAD using Cox proportional hazards regression within a cohort of 53,416 Swedish adults. Replication was sought in a case-control study of 28,123 PAD cases and 128,459 controls from the VA Million Veteran Program (MVP) and a cohort study of 452,028 individuals from the UK Biobank (UKB). Two-sample Mendelian randomization (MR) was used to estimate causal effects of sleep-related traits on PAD (31,307 PAD cases 211,753 controls). Results: Observational analyses demonstrated a U-shaped association between sleep duration and PAD risk. In Swedish adults, incident PAD risk was higher in those with short sleep (&lt;5 hours; hazard ratio (HR) 1.74; 95% confidence interval (CI) 1.31-2.31) or long sleep (≥8 hours; HR 1.24; 95% CI 1.08-1.43), compared to individuals with a sleep duration of 7 to &lt;8 hours/night. This finding was supported by case-control analysis in MVP and cohort analysis in UKB. Observational analysis also revealed positive associations between poor sleep quality (HR 1.81; 95% CI 1.13-2.90) and daytime napping (HR 1.32; 95% CI 1.18-1.49) with PAD. MR analysis supported an inverse association between sleep duration (odds ratio per hour increase, 0.79, 95% CI, 0.55, 0.89) and PAD, and an association between short sleep and increased PAD (odds ratio, 1.20, 95% CI, 1.04-1.38). MR also found an association between insomnia with PAD (OR 1.10; 95% CI 1.05-1.15) and a reverse association of PAD on shorter sleep (OR 1.05; 95% CI 1.01-1.10). Conclusions: Short sleep duration and measures of poor sleep quality may be causal risk factors for PAD. Maintenance of healthy sleep habits may help prevent PAD.